Microsomal Ca²⁺ flux modulation as an indicator of heavy metal toxicity

Inositol 1,4,5-trisphosphatee (IP3), an intracellular messenger, releases Ca²⁺ from microsomes. Ca²⁺ plays a major role in regulating various cellular events like neural transmission and regulation of hormones and growth factors. Aluminum (Al), lead (Pb) and mercury (Hg) were reported to alter Ca²⁺-regulated events thereby causing neurotoxicity. Hence, an attempt was made characterize IP3 mediated Ca²⁺ release from rat brain microsomes under the influence of Al, Pb and Hg. Different concentrations of metals were tested over a designated time scale and their effects on IP3 mediated Ca²⁺ release from microsomes were monitored using Fura-2 technique. All the three metals inhibited IP3 mediated Ca²⁺ release, Pb being more potent. The order of potency of these three metals was Pb>Hg>Al. Except for Al, both Hg and Pb independently released Ca²⁺ from microsomes. Re-uptake of Ca²⁺ into microsomes was inhibited by all the three metals, Pb being more potent. Microsomal Ca²⁺-ATPase activity was also inhibited by all the three metals. These results suggest that neurotoxicity exerted by Al, Pb and Hg may be due to the interference of these metals with IP3 mediated calcium release and also interfering with the microsomal Ca²⁺ sequestration mechanism. Differential effects of heavy metal induced changes in Ca²⁺ flux can be used as an index of relative toxicity.